Process for the purification of thermolabile compounds by distillation

ABSTRACT

The invention relates to a new process for the purification, by distillation, of thermolabile compounds wherein a thermolabile compound is introduced into a twin screw extruder which is heated, in at least one zone, to the boiling temperature of the compound. The volatilized compound is drawn off and condensed.

The invention relates to a process for the preparation and purificationof thermolabile viscous compounds, in particular glycolides.

In the context of the invention, glycolides are the cyclic six-membereddiesters of α-hydroxycarboxylic acids of the general formula ##STR1##wherein R₁ and R₂ which can be identical or different, can denotehydrogen or a branched or unbranched alkyl radical with up to 16 carbonatoms, such as e.g. methyl, ethyl, n-propyl, iso-propyl, n-butyl,iso-butyl, tert.butyl and others.

Glycolides, in particular glycolide (1,4-dioxane-2,5-dione) itself, andlactides are used, inter alia, as starting substances for thepreparation of biologically degradable medical auxiliary materials basedon polyesters. Both polyglycolide (1,4-dioxane-2,5-dione) andpolylactide themselves and the copolymers of lactides with otherglycolides, in particular 1,4dioxane-2, 5-dione and other reactionpartners capable of polymerization, are used.

The preparation of glycolides is described in the literature.

Examples of known preparation processes for glycolide(1,4-dioxane-2,5-dione) are those based on glycolic acid (DE-A-16 68 993and DE-A-16 68 994), halogenoacetic acids (F. Andreas et al., J. Pr.Chem. 18, 141 (1962)) and salts thereof, polyglycolic acid, glycolicacid esters (FR 14 85 302), chloroacetyl-glycolic acid salts (US-A-37 63190) and chloroacetylpolyglycolic acid (J. Am. Chem. Soc. 76, 754(1954)), or, generally, preparation processes based onα-halogenocarboxylic acids, α-hydroxycarboxylic acids and derivativesthereof, such as e.g. α-hydroxycarboxylic acid esters, andpoly-α-hydroxycarboxylic acids. In the case of the monomeric educts, apolyester is first formed, and is then subjected, in situ or afterisolation, to further reaction to give the dimer. This reaction consistsof thermolysis at 200°-300° C. with the addition of metals, metal oxidesor salts. The dimers thereby formed are distilled off--preferably undera vacuum. The distillate is converted into a stable form in purificationsteps which are to be carried out several times, such as e.g.crystallization from suitable solvents. Such a procedure is describedfor lactide, for example, in British Patent No. 1 007 347.

The thermolysis disclosed in that patent is, because of the propertiesof the starting material and reaction product, a hazardous reactionwhich is to be classified as a reaction with a high safety risk due tothe possible danger of explosion. The thermodynamic study of thereaction shows that the reaction temperature required for formation ofglycolide from polyglycolic acid or of lactides from polylactic acidslies in in the region of thermal decomposition of the compounds to givegaseous secondary products. The exothermicity of the decompositionreaction is compensated by the vaporization enthalpy of the glycolidesformed. It follows that the reaction can then lead to thermo-explosionof the reaction mixture if the vaporization of the glycolides forwhatever reason--is no longer guaranteed, such as e.g. in the event of abreakdown in the vacuum, blockage of the lines etc. The course of theconventional thermolysis process under batch conditions is outlinedbelow using the example of glycolide or lactide.

The low molecular weight polylactic acid (polyglycolic acid) used as thestarting substance is mixed with the catalyst and the mixture isintroduced into the reaction apparatus and heated up to the requiredreaction temperature of 240°-260° C. During the heating up operation,the starting substance melts, and at 240° C. the lactide (glycolide)starts to distil off. After a short time the reaction mixture becomesdark in colour and is transformed into a viscous state. From this pointin time, the reaction mixture is no longer perfectly homogenised. Theinhomogeneous reaction mixture tends towards uncontrolled decomposition,since local foci of overheating may develop. The reaction residue whichremains in the reaction mixture when the reaction has ended must beremoved from the reaction vessel by prolonged heating in concentratedsodium hydroxide solution.

Because of the inhomogeneous reaction conditions, varying qualities andyields are achieved in batchwise thermolysis. The yield of distillate,i.e. of crude lactide, is 70-90% of theory t.q. After working up of thedistillate by precipitation in a suitable organic solvent, such as e.g.alcohols (C₁ to C₄) or halogenated hydrocarbons (e.g. carbontetrachloride), a yield of 40-60% of theory is obtained. DE-A-15 43 958quotes a yield of, for example, 56% in the thermolysis, but thesubsequent purification steps have not yet been taken intoconsideration.

Surprisingly, the disadvantages described above for the preparationprocess known from the literature can be avoided with the processaccording to the invention.

The process is characterized in that the reaction is carried outcontinuously under forced conveyance into a reactor with a risingtemperature gradient.

The product formed in the thermolysis is collected as the distillate andoptionally subjected to further purification steps. Unreacted startingmaterial and higher-boiling by-products are discharged from the reactoras a result of the forced conveyance.

The reaction can conveniently be carried out under an inert gasatmosphere and/or reduced pressure.

A suitable reactor such as can be used according to the invention is,for example, a self-cleaning twin-screw extruder with attached exhaustvapour lines.

Such apparatuses are known and find many applications in plasticsproduction. The apparatuses are as a rule constructed by the modularprinciple and are marketed by a number of machine construction companiesin comparable forms. Whereas in the plastics processing industrytwin-screw extruders are used for homogenizing plastics granules, ifappropriate with admixing of auxiliaries, such as fillers or pigments,and for generating the necessary admission pressure at the shaping die,in the case of the preparation of glycolides the extruder is used as acontinuously operating chemical reactor.

The following advantages over known preparation processes resultaccording to the invention.

As a result of the low thermolysis volume, the reaction mass is keptsmall. Trouble or hazards due to pressure build-up during the reactionare therefore insignificant and require no special measures. The twinscrew of the extruder ensures on the one hand perfect homogenisation ofthe reaction mixture and thus a uniform reaction temperature over thecross-section of the flow tube, and on the other hand forced dischargeof the polymeric material always formed by side reactions, andfurthermore a suitable arrangement of the twin screw ensures continuousself-cleaning of the reactor, which means that sticking of the reactionmixture to components of the reactor is avoided, since the residue istransported forcefully by the twin screw into the residue tank. Acontinuous thermolysis procedure is thereby rendered possible. The twinscrew of the extruder furthermore ensures perfect homogenization of thereaction mixture and thus a constant, controlled temperature programme.

The construction of such an extruder is shown schematically in FIG. I.

This figure illustrates the principle of the reaction procedure in theflow tube with forced conveyance in a twin-screw extruder.

The extruder has devices which allow separate heating of the individualsegments, so that a temperature gradient can be built up, heating beingcarried out, for example, according to the following plan:

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The number of heating segments can of course be varied if a moredifferentiated temperature programme is required.

The exhaust vapour lines with which the product is collected asdistillate are located above housings no. 7 and 8. The apparatusfurthermore consists of a reservoir tank and a residue tank, and ofdevices for maintaining a vacuum. The starting material is conveyed viaa metering screw into the actual reactor, in which a twin screw on theone hand effects forced conveyance through the reactor and on the otherhand ensures homogeneous mixing of the plastic reaction mixture and alsoself-cleaning during the entire course of the reaction.

DESCRIPTION OF THE PROCESS

The poly-hydroxycarboxylic acids used in the depolymerization reactionare prepared as described in the literature, see e.g. Chem. Ber. 58,1307 (1925).

For example, commercially available optically active [R], [S] or racemiclactic acids are dehydrated by distillation under a vacuum up to a sumptemperature of 200° C. Oligomeric lactic acids are thereby formed. Theselactic acids are liquid at elevated temperature and solidify on coolingto room temperature to give vitreous masses which can be comminuted bythe customary mechanical methods. The powders or granules obtained inthis way are mixed with a suitable catalyst and the mixture isintroduced into the product feed of the extruder using a solids dosagedevice.

The twin screw conveys the reaction mass through the flow tube. Behindthe screw, by suitable choice of the speed, feed and temperature, aconsistency of the reaction mass is established such that a vacuum of2-5 mbar on the distillation side is maintained. The backpressure in theflow tube can be brought about by suitable choice of the screwconfiguration, e.g. by changing the screw pitch, or by reversing theconveying direction. (FIG. I shows the screw configuration of a screwschematically; the expert is sufficiently familiar with the technicalrealization of a corresponding self-cleaning twin screw.) The reactionmass then passes through a temperature gradient of 130°-280° C.Thermolysis of the low molecular weight polyglycolide to give glycolidethereby takes place. Evaporation takes place under the exhaust vapouropenings, the resulting distillate is removed to a heated reservoir tankand the residue which remains makes up about 5 wt.% of the amountintroduced and is conveyed forcedly by the screw into the residuedischarge tank, so that continuous operation is rendered possible. Incarrying out the process, it proves to be advantageous if the heatingsegment after the exhaust vapour lines (heating segment 9 in FIG. I) hasa lower temperature than that on the exhaust vapour lines; this ensuresthat the polymeric material formed by side reactions is solidified anddischarged. If desired further exhaust vapour lines can be attached inregions of lower temperatures in order to remove low-boiling impurities.

The process described above can be carried out on an industrial scale.The yield of distillate (crude glycolide) is about 95.0% of theory t.q.

DESCRIPTION OF THE APPARATUS

The extruder is equipped with a metering screw for feeding in solid onthe feed side, and furthermore with a heated exhaust vapour tube, acondenser, two interchangeable vacuum receivers for vacuum distillationand a vacuum-proof discharge tank which collects the reaction residue.Details of the apparatus can be seen from the flow chart included forthe process (FIG. I). The apparatus also has devices for generating andmaintaining the necessary vacuum of 2 to 5 mbar. The segments 0 to 9designate parts of the reactor which can be heated independently of oneanother, which means that the necessary temperature gradient can beproduced.

The screw is designed so that, as a result of the plastic material, avacuum can be maintained without problems in a certain section of thereactor. FIG. I illustrates the pressure pattern within the reactor.

Glycolides of the general formula I wherein R₁ and R₂ have the meaningsgiven below are preferably prepared in the process according to theinvention.

    ______________________________________                                        R.sub.1                                                                            H         H        CH.sub.3                                                                              C.sub.2 H.sub.5                                                                      CH(CH.sub.3).sub.2                     R.sub.2                                                                            H         CH.sub.3 CH.sub.3                                                                              H      H                                      R.sub.1                                                                            C.sub.2 H.sub.5                                                                         n-C.sub.4 H.sub.9                                                                      C(CH.sub.3).sub.3                                                                     nC.sub.5 H.sub.11                                                                    nC.sub.7 H.sub.15                      R.sub.2                                                                            CH.sub.3  H        H       H      H                                      R.sub.1                                                                            n-C.sub.12 H.sub.25                                                                     n-C.sub.15 H.sub.31                                                                    n-C.sub.13 H.sub.27                                                                   n-C.sub.14 H.sub.29                           R.sub.2                                                                            H         H        H       H                                             R.sub.1                                                                            n-C.sub.16 H.sub.33                                                      R.sub.2                                                                            H                                                                        ______________________________________                                    

To prepare glycolide (1,4-dioxane-2,5-dione) in the process according tothe invention, a low molecular weight (oligomeric) polyglycolide or ahalogenoacetic acid salt, for example, is used as the starting materialand is introduced into the reservoir tank (see FIG. I) together with asuitable catalyst. The preparation of low molecular weight polyglycolideis generally known, and is thus carried out e.g. by heatinghalogenoacetic acids and/or sodium chloroacetate in xylene. Suitablecatalysts for the depolymerization are likewise prior art, for exampletin and zinc or their compounds. A preferred catalyst is zinc oxide.Between 0.01 and 4 wt.% catalyst is in general used. The educts are thenintroduced into the extruder by means of a metering screw and arereacted as described above.

The thermolysis in the process described above can be transferred to theindustrial scale. The yield of distillate (crude glycolide) is 95% oftheory t.q. After working up by precipitation in isopropanol, a yield of81% of theory results. The increase in yield over the batch process ison average about 60%. The product is passed to a further purificationprocess which leads to a glycolide quality which is suitable for thepreparation of high molecular weight polyesters such as are used e.g.for the production of surgical suture material.

The new process carried out in a self-cleaning flow tube with forcedconveyance (twin-screw extruder) is distinguished in particular by thefollowing advantages over the processes described in the literature:

problem-free practicability of the reaction due to the forced dischargeof polymeric material formed,

higher yield,

better product quality,

high safety in carrying out this reaction with a high hazard classbecause of the very small thermolysis volume in the flow tube and theresulting very small reaction mass,

very low-polluting.

As a result of the high yield and the special process technology, onlyminimal amounts of solid waste products are obtained. The large amountsof strongly alkaline effluents formed in the batch process are avoided.

The new continuously operating process now renders it possible toprepare glycolides in a conventionally equipped chemical factory withoutparticularly expensive safety installations.

The above-mentioned preparation process is also suitable for thedistillation of chemical compounds.

Distillation is a widely used method of purifying or separating organicand inorganic chemical substances (see R. Billet, "IndustrielleDestillation" [Industrial Distillation], Verlag Chemie, Weinheim, 1973).

Distillations are frequently carried out under a vacuum, in order toreduce the exposure of the substances to heat by reducing the boilingpoint. Various technical embodiments belong to the prior art, includingapparatuses for carrying out vacuum distillation by a continuousprocess. Apparatuses which permit the gentlest possible vacuumdistillation of chemical substances are e.g. thin film evaporators andfalling film evaporators of various construction and design. Thesedistillation processes are used both for substance distillation in theactual sense and for removing more highly volatile secondaryconstituents, such as solvents or, in the case of polymeric substances,residual monomer. The desired product is found in the distillationresidue in these cases. In cases where highly volatile constituents areto be removed from highly viscous mixtures by distillation, screwevaporators are also used in exceptional cases in industry (see Ullmann,"Enzyclopadie der technischen Chemie" (Encylopaedia of IndustrialChemistrv), Volume 2, page 658 et seq.). Volatilization of monomers frompolymeric material with the aid of screw evaporators is described, forexample, by K.-M. Hess in Chem. Ing. Techn. 51 (3), 245 (1979).

The distillation of chemical substances in general finds its limitswhere the substances can no longer be evaporated without decompositionand high-boiling and highly viscous or solid, often polymericby-products are formed by the decomposition content. In industrialdistillation processes, these by-products lead to a number of problems,the cause of which lies in the formation of deposits (fouling) on thesurfaces of the distillation apparatuses and heat exchangers. Heattransfer is impaired by deposit formation at the edges, and uniformevaporation of the substance no longer takes place. This fouling processis of great disadvantage particularly in all types of continuousevaporators, but especially in the continuous falling or climbing filmevaporators of various design.

Surprisingly, it has been possible to eliminate the abovementioned knowndisadvantages in the distillation of thermolabile compounds usingconventional processes by a procedure in which the substance to bedistilled is distilled in a reactor (flow tube) with a risingtemperature gradient under forced conveyance.

The process according to the invention is distinguished by the fact thatchemical compounds which tend to decompose during distillation can bedistilled, even at higher temperatures, optionally under a vacuum, withexcellent yields and a reduced safety risk.

A number of substances, in particular organic compounds, which can bedistilled in evaporators of the conventional type only with a poor yieldand/or only under a high safety risk, if at all, can thus be distilledat a high temperature under a high vacuum within the thermaldecomposition range of the substances.

The process according to the invention is described in more detailbelow. In the process according to the invention, the substance isdistilled in a continuous process in a flow tube with forced conveyance,optionally under reduced pressure, optionally under an inert gasatmosphere, and under a rising temperature gradient. The substance isthereby conveyed with a very short residence time along a temperaturegradient, whereupon it evaporates. The distillate is then precipitatedwith the aid of a suitable condenser system and isolated.

In a preferred embodiment, the flow tube consists of a twin-screwextruder, the twin screw taking over the functions of sealing off thevacuum from the atmosphere, forced conveyance and self-cleaning. Thefouling deposit is removed from the heat-transferring walls by the twinscrew and conveyed to the residue discharge tank.

The construction of an extruder which can be used for the distillationhas already been shown essentially in FIG. I, but there are differencesin the heating of the individual segments.

FIG. II shows schematically the construction of an extruder which issuitable for distillations.

The extruder has devices which allow separate heating of individualsegments, so that a temperature gradient can be built up, heating beingcarried out, for example, in accordance with the following plan:

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The exhaust vapour lines with which the distillate is collected arelocated above housings no. 7 and 8. The apparatus furthermore consistsof a reservoir tank and a residue tank, and of devices for maintaining avacuum. The substance to be distilled is fed from the reservoir tankinto the flow tube, where it is heated to the boiling point as a resultof forced conveyance, e.g. by a synchronously rotating twin screw,through segments of increasing temperature. The temperature programmedepends on various factors, such as e.g the construction of the reactor(extruder), the speed, amount and nature of the material introduced,etc. In the region of the boiling point, the distillate is removed,whilst the higher-boiling residue is removed from the distillationregion as a result of the forced conveyance. For carrying out theprocess, it is advantageous if the heating segments downstream of theexhaust vapour lines have a temperature below the boiling point of thedistillate, so that the distillation residue solidifies when it isdischarged as a result of the forced conveyance. Behind the screw, bysuitable choice of the speed, feed and temperature, a consistency of thereaction mass can be established (see FIG. I) such that a reducedpressure can be maintained on the distillation side.

The backpressure in the flow tube can be brought about by suitablechoice of the screw configuration, e.g. by changing the screw pitch, orby reversing the conveying direction. (FIG. I shows the screwconfiguration of a screw schematically; the expert is sufficientlyfamiliar with the technical realization of a corresponding self-cleaningtwin screw.) The resulting distillate is condensed and, optionally,further processed.

The number of heating segments, the temperature programme, the speed ofthe screw and the location and number of the exhaust vapour lines can ofcourse be adapted to suit the specific distillation problem.

The process according to the invention is not limited exclusively to thedistillation of liquid or viscous substances. Because of the forcedconveyance of the substance, plastic or solid compounds can also bedistilled or sublimed. It goes without saying here that the heating ofthe exhaust vapour line and also its construction is designed so thatcondensation of the product does not lead to blocking of the apparatusand, for example, first occurs in a suitable cold trap.

The temperature of the heating segments is determined by the heatingmedium used. Heating of the segments by oil follows. If the maximumheating segment temperature is about 300° C., about 400° C. can beachieved if electrical heating is used. Such heating systems are alreadycommercially available. However, for specific problems, it is alsoconceivable to use specially manufactured products with segments whichcan be heated to higher temperatures. The distillation can be carriedout under reduced pressure in order to reduce the boiling points.Depending on the construction, pressures down to a lower limit of about0.5 mbar can be established.

The distillation process described above is suitable not only for thelaboratory scale but also for distillations on an industrial scale.

The new process permits high temperature distillation of organiccompounds of low volatility by a continuous procedure. The distillationprocess according to the invention is particularly suitable for thepurification of compounds with which a higher-boiling componentconcentrates in the bottom product as an undesirable by-product inconventional distillation processes. The process is also suitable fordistilling compounds off from solid residues.

The possibility is therefore provided of distilling, and hencepurifying, without danger and in a high yield, substances which cannotbe distilled under conventional conditions because of theirthermolability.

In cases where recrystallization--sometimes several times--can bereplaced by the new process, the environmental benefit of thedistillation process is a further additional advantage:

Only very small amounts of residues, if any, are obtained, no emissionarises and the effluent is not polluted.

The following examples are intended to illustrate the process accordingto the invention in more detail.

1. Apparatus

Twin-screw metering unit for solids

Twin-screw extruder with exhaust vapour removal and vacuum connection

Glass condenser charged with heat transfer medium

Vacuum receiver with double jacket

Residue discharge tank with nitrogen compensation and vacuum connection

2. Process procedure

The extruder is heated in accordance with the temperature gradientsgiven in the examples.

The exhaust vapour line is heated to the desired temperature and thedouble-jacketed glass receivers are heated with heat transfer medium toa temperature above the melting point of the appropriate compound.

When the desired temperature is reached, the extruder is operated withthe normal feed, as mentioned in the example, and the normal screwspeed. The pressure during the distillation is 0.5 to 1,025 mbar,preferably 2-10 mbar. After flushing of the vacuum receivers withnitrogen, the distillate is drained off into a thermal vessel and passedto a suitable method of working up, such as e.g. granulation in anon-solvent or solidification by cooling by means of a belt or rollers.

The process according to the invention is particularly suitable for thepurification of glycolide (1,4-dioxane-2,5-dione), a glycolide of veryhigh purity which can be used for polymerization without furtherpurification measures being obtained.

The condensed distillate of pure glycolide obtained by the processaccording to the invention is then precipitated in a non-solvent, e.g.petroleum ether. The crystal suspension thus obtained is separated offand dried. It is also possible, and desirable on an industrial scale, toallow the distillate to solidify directly via a cooling device, such ase.g. a cooling roller or cooling belt. The indirect route viagranulation in an inert solvent and the subsequent separation and dryingstep is thereby avoided.

If desired, or if it appears to be necessary, low-boiling impurities ofthe crude glycolide can be removed by additional exhaust vapour lines inthe lower temperature regions.

The process according to the invention renders possible the continuousdistillation of crude glycolide on an industrial scale, between 95 and98 wt.% (based on the crude glycolide employed) highly pure glycolidesuch as it has not been possible to prepare in this purity on anindustrial scale by processes known hitherto being obtained.

The purification processes known from the prior art, whetherrecrystallisation or sublimation, give a glycolide which differs in itssubstance properties from the glycolide prepared by the processaccording to the invention. Thus, for example, batchwise distillationprocesses cause a greater exposure of the glycolide to heat and lead toa higher content of decomposition products, which are also deposited onthe cooling surface during sublimation and can no longer be removed fromthe glycolide.

Whereas a glycolide (1,4-dioxane-2,5-dione) prepared by knownpurification processes can be polymerised to give a polyglycolide withan intrinsic viscosity of about 1 [dl/g], a polyglycolide with anintrinsic viscosity of>1.4 [dl/g] is obtained under identicalpolymerization conditions (e.g. SnC12 ×H20, lauryl alcohol) from aglycolide prepared by the process according to the invention. (Theintrinsic viscosities are determined in hexafluoroisopropanol at 30°C.).

EXAMPLE 1

Continuous preparation of glycolide from low molecular weightpolyglycolide with catalytic amounts of zinc oxide

2 wt.% zinc oxide is added to low molecular weight polyglycolide and themixture is homogenised in a suitable mixing apparatus, such as e.g. agyrowheel mixer.

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The extruder is heated in accordance with the above table (see also FIG.I), the exhaust vapour line is heated at 180° C. and the vacuumreceivers for collecting the distillate are heated at 80° C.

When the desired temperature is reached, the extruder is operated at aspeed of 1.67/sec and a feed of 3.0 kg/hour low molecular weightpolyglycolide under a pressure of 2-5 mbar. The vacuum receivers areemptied after periods of 60 minutes and the distillate is worked up. Theyield of distillate is 95% of theory. The distillate is worked upconventionally by batchwise reprecipitation from isopropanol in a ratioof distillate/isopropanol=1/2.5.

EXAMPLE 2

Continuous preparation of glycolide from sodium chloroacetate withcatalytic amounts of zinc oxide

2 wt.% zinc oxide is added to sodium chloroacetate and the mixture ishomogenised in a suitable mixing apparatus, such as e.g. a gyro-wheelmixer.

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The extruder is heated in accordance with the above table (see also FIG.I), the exhaust vapour line is heated at 180° C. and the vacuumreceivers for collecting the distillate are heated at 80° C.

When the desired temperature is reached, the extruder is operated at aspeed of 1.33/sec and a feed of 3.3 kg/hour sodium chloroacetate under apressure of 2-5 mbar. The vacuum receivers are emptied after periods of60 minutes and the distillate is worked up as described in Example 1.

EXAMPLE 3

Continuous preparation of [S,S]-lactide from [S]-polylactic acid withcatalytic amounts of zinc oxide 2 wt.% zinc oxide is added to[S]-polylactic acid and the mixture is homogenised in a suitable mixingapparatus, such as e.g. a gyro-wheel mixer.

The extruder is heated in segments at from 15 to 285° C. The exhaustvapour line is heated at 170° C. and the temperature of the vacuumreceivers for collecting the distillate is 90° C. When the desiredtemperature is reached, the extruder is operated at a speed of 2.5/secand a feed of 2.5 kg/hour [S]-polylactic acid under a pressure of 2-5mbar. The vacuum receivers are emptied after periods of 60 minutes andthe distillate is worked up.

The yield of distillate is 95% of theory. The distillate is worked up bybatchwise reprecipitation from isopropanol in a ratio ofdistillate/isopropanol =1/1.5.

EXAMPLE 4

Continuous preparation of [R,R]-lactide from [R]-polylactic acid withcatalytic amounts of zinc oxide.

The preparation of the enantiomeric lactide follows the same procedureas described above for the optical antipode [S,S]-lactide.

EXAMPLE 5

Continuous preparation of [R,R],[S,S]-lactide (racemic lactide) and[R,S]-lactide (meso-lactide) from [R],[S]-polylactic acid with catalyticamounts of zinc oxide

The preparation of the mixture of [R,R],[S,S]-lactide (racemic lactide)and [R,S]-lactide (meso-lactide) follows the same procedure as describedfor [S,S]-lactide. The racemic lactide and meso-lactide are separated ina separate working up step.

EXAMPLE 6

Continuous distillation of [S,S]-3,6-dimethyl-1,4-dioxane-2,5-dione

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The exhaust vapour line is heated at 140° C. and the double-jacketedglass receivers are heated at 95° C. with hot water.

When the desired temperature is reached, the extruder is operated with afeed of 5 kg per hour [S,S]-3,6-dimethyl-1,4-dioxane-2,5-dione at ascrew speed of 1.67/sec. The pressure during the distillation is 2-4mbar. After flushing with nitrogen, the distillate is drained into athermal vessel and precipitated in petroleum ether 60/90 in a ratio of1/4 in a universal apparatus. The solid is removed via a centrifuge anddried in a vacuum drying cabinet.

The yield is 95-98% of the feed material.

EXAMPLE 7

Continuous distillation of [R,R]-3,6-dimethyl-1,4-dioxane-2,5-dione

The distillation of the [R,R] enantiomer of3,6-dimethyl-1,4-dioxane-2,5-dione follows the instructions given inExample 3 for the [S,S] enantiomer of lactide.

EXAMPLE 8

Continuous distillation of[R,R],[S,S]-3,6-dimethyl-1,4-dioxane-2,5-dione

The distillation of the racemate of 3,6-dimethyl-1,4-dioxane-2,5-dionefollows the instructions given in Example 3 for the [S,S] enantiomer

EXAMPLE 9

Continuous distillation of [R,S]-3,6-dimethyl-1,4-dioxane-2,5-dione

The distillation of meso-3,6-dimethyl-1,4-dioxane-2,5-dione follows theinstructions given in Example 3 for the [S,S] enantiomer of lactide.

EXAMPLE 10

Continuous distillation of 3-hydroxyacetophenone

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The exhaust vapour line is heated at 170° C. and the double-jacketedglass receivers are heated at 90° C. with hot water.

When the desired temperature is reached, the extruder is operated with afeed of 4.3 kg per hour 3-hydroxy- acetophenone at a screw speed of2.5/sec. The pressure during the distillation is 2-4 mbar. Afterflushing with nitrogen, the distillate is drained into a thermal vesseland precipitated in water in a ratio of 1/2 in a universal apparatus.The solid is separated off via a centrifuge and dried in a circulatingair drying cabinet.

The yield is 91% of the feed.

EXAMPLE 11

Continuous distillation of 3-amino-2-chloropyridine

    ______________________________________                                        Housing 0     1     2   3   4   5    6    7    8    9                         no.                                                                           Tempera-                                                                              15    50    65  70  80  130  130  130  130  120                       ture [°C.]                                                             ______________________________________                                    

The exhaust vapour line is heated at 130° C. and the double-jacketedglass receivers are heated at 80° C. with hot water.

When the desired temperature is reached, the extruder is operated with afeed of 3.2 kg/hour 3-amino-2-chloropyridine at a screw speed of0.83sec. The pressure during the distillation is 2-4 mbar. Afterflushing with nitrogen, the distillate is drained into a thermal vesseland precipitated in water in a ratio of 1/1.4 in a universal apparatus.The solid is separated off via a centrifuge and dried in a circulatingair drying cabinet. The yield is 85% of the feed.

EXAMPLE 12

Continuous distillation of glycolide (1,4-dioxane-2,5-dione)

    __________________________________________________________________________    Housing no.                                                                             0  1  2  3  4  5  6  7  8  9                                        Temperature [°C.]                                                                15 50 70 140                                                                              190                                                                              200                                                                              200                                                                              200                                                                              190                                                                              190                                      __________________________________________________________________________

The exhaust vapour line is heated at 140° C. and the double-jacketedglass receivers are heated at 85° C. with hot water. When the desiredtemperature is reached, the extruder is operated with a feed of 5 kgglycolide per hour at a screw speed of 1.67/sec. The pressure during thedistillation is 2-4 mbar. After flushing with nitrogen, the distillateis drained into a thermal vessel and precipitated in petroleum ether60/90 in a ratio of 1:4 in a 50 liter apparatus. The crystal suspensionthus obtained is separated off via a centrifuge and dried in a vacuumdrying cabinet. The yield is 95-98% of the feed. Material is suitablee.g. for the production of suture materials.

    ______________________________________                                        Product description:                                                          Appearance:      white crystals                                               Smell:           almost odourless                                             Identity:        IR: α-form                                             Solubility:      readily soluble in acetone                                                    sparingly soluble in toluene                                 H.sub.2 O (Karl Fischer): 0.01%                                               Heavy metals:    >10 ppm                                                      Free acid:       0.02%                                                        Content:         99.8%-100.0%                                                 Melting point:   84.1° C.                                              (Differential thermal                                                         analysis)                                                                     ______________________________________                                    

What is claimed is:
 1. A method for purifying a thermolabile compound bydistillation which comprises:(a) introducing the thermolabile compoundto be purified into the first end of a twin screw extruder having afirst end and a second end, twin screws for conveying material throughthe extruder from the first end toward the second end, at least onevolatilization zone between the first and second ends of the extruderwhich is heated to the boiling point of the compound to be purified and,at least one exhaust vapor line located in the area of the saidvolatilization zone or zones for removing volatilized compound from theextruder; (b) conveying the compound from said first end of the extrudertoward the second end thereof by means of the twin screws therein,whereby the compound passes through the volatilization zone or zones,thereby volatilizing the compound; (c) drawing off the volatilizedcompound through the exhaust vapor lines; and, (d) condensing thevolatilized compound thus drawn off.
 2. The method of claim 1 whereinthere is a rising temperature gradient within the extruder, with thetemperature increasing from the first end to the said volatization zoneor zones.
 3. The method of claim 1 wherein the distillation is carriedout under reduced pressure and concomitantly reduced temperature.
 4. Themethod of claim 2 further characterized in that the temperaturedownstream of the said volatilization zone or zones is lower than thatof the said volatilization zone or zones.
 5. The method of claim 1further characterized in that the compound to be purified is a compoundof the formula ##STR2## wherein R₁ and R₂ independently of one anotherare hydrogen or an branched or unbranched alkyl of 1 to 16 carbon atoms.6. The method of claim 5 characterized in that the compound is1,4-dioxane-2,5-dione or lactide.